Relationship between periparturient diseases, metabolic markers and the dynamics of hair cortisol concentrations in dairy cows.

Hair cortisol concentration (HCC) might represent a promising marker for retrospective welfare assessment of dairy cows. The objective of the study was to explore the dynamics of HCC in diseased and healthy cows from eight-week ante partum (AP) to eight-week post partum (PP). Twenty-four pregnant cows were followed from drying off to week eight PP. Tail hair was used to measure cortisol at five different time points. The occurrence of peripartum diseases, lameness and the body condition score (BCS) were monitored on a weekly basis. Blood ß-hydroxybutyric acid, non-esterified fatty acids, calcium and insulin-like growth factor-1 (IGF-1) concentrations were measured. The temperature-humidity index (THI) was continuously recorded. The median values of HCC in all cows were 0.4, 0.3, 0.6, 0.8 and 0.5 pg/mg at weeks eight, four AP, calving, weeks four, eight PP, respectively. There was no association between HCC and the occurrence of peripartum diseases (P ≥ 0.05). A positive correlation between HCC and BCS loss (P < 0.01) and THI (P < 0.05) was observed. The occurrence of peripartum diseases was associated with low IGF-1 during the study period but no relationship was found between cortisol and IGF-1 levels (P ≥ 0.05). Brown Swiss cows showed higher HCC (P < 0.01) at weeks eight, four AP, and week four PP and lower average milk yield (P < 0.05) than Holstein-Friesian cows. In conclusion, HCC was not a suitable marker for peripartum diseases but it could reflect a stress response, which is linked to BCS loss, heat stress and breed.

Biallelic KITLG variants lead to a distinct spectrum of hypomelanosis and sensorineural hearing loss.

BACKGROUND: Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper- and hypopigmentation, all of which are inherited in an autosomal dominant manner. OBJECTIVES: To describe the genotypic and clinical spectrum of biallelic KITLG-variants. METHODS: We used a genotype-first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports. RESULTS: We describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a 'sock-and-glove-like', symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss-of-function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory-pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism. CONCLUSIONS: We provide consolidating evidence that biallelic KITLG variants cause a distinct auditory-pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT-related piebaldism.

SARS-CoV-2 vaccine-associated subacute thyroiditis.

PURPOSE: With coronavirus disease 2019 (COVID-19), subacute thyroiditis (SAT) cases are on the rise all over the world. COVID-19 vaccine-associated SAT cases have also been reported. In this article, we present our data on 11 vaccine-associated SAT cases. METHODS: Eleven patients were included in the study. Type of the vaccines patients received, time to the occurrence of SAT after vaccination, symptoms and laboratory findings, treatment given, and response to treatment were evaluated. RESULTS: The age of patients ranged from 26 to 73. Four of the patients were males, and seven were females. Symptoms of six patients were seen after BNT162b2 Pfizer/BioNTech COVID-19 mRNA vaccine®, and four of them after Coronavac inactivated SARS-CoV-2 vaccine®. In one patient, SAT developed after the first dose of BNT162b2, administered after two doses of Coronavac. The average time to the onset of symptoms was 22 days (15-37) after vaccination. CONCLUSIONS: The fact that both whole virus containing and genetic material containing vaccines cause SAT suggests that the trigger may be viral proteins rather than the whole viral particle. Although corticosteroids are commonly preferred in published vaccine-associated SAT cases, we preferred nonsteroidal anti-inflammatory therapy in our patients for sufficient vaccine antibody response. There is not enough information about whether patients who develop SAT can be revaccinated safely considering the ongoing pandemic. Further research is needed for a conclusion in the treatment and revaccination of these patients.

Evaluation of the academic productivity of the top 100 worldwide physicians in the field of otorhinolaryngology and head and neck surgery using the Google Scholar h-index as the bibliometrics ranking system.

OBJECTIVE: The top 100 physicians of otorhinolaryngology and head and neck surgery worldwide were investigated using the Google Scholar h-index. METHOD: Although there are various bibliometrics ranking systems that present the academic quantity and quality of scientists' published articles, the h-index is the most popular and widely accepted. In this study, Google Scholar was used to search all the keywords involving all the subspecialties of otorhinolaryngology and head and neck surgery, with the aim of identifying as many physicians as possible. Obtaining the Google Scholar h-index and citations is not possible for scientists who do not have Google Scholar accounts. Thus, only those with Google Scholar accounts were included. RESULTS: The average h-index of all 100 physicians enrolled in the study was 37.83, with a range of 25-81. CONCLUSION: The current study details the academic impact of otorhinolaryngology and head and neck surgery physicians worldwide based on the Google Scholar h-index.

Variants in CIB2 cause DFNB48 and not USH1J.

The genetic, mutational and phenotypic spectrum of deafness-causing genes shows great diversity and pleiotropy. The best examples are the group of genes, which when mutated can either cause non-syndromic hearing loss (NSHL) or the most common dual sensory impairment, Usher syndrome (USH). Variants in the CIB2 gene have been previously reported to cause hearing loss at the DFNB48 locus and deaf-blindness at the USH1J locus. In this study, we characterize the phenotypic spectrum in a multiethnic cohort with autosomal recessive non-syndromic hearing loss (ARNSHL) due to variants in the CIB2 gene. Of the 6 families we ascertained, 3 segregated novel loss-of-function (LOF) variants, 2 families segregated missense variants (1 novel) and 1 family segregated a previously reported pathogenic variant in trans with a frameshift variant. This report is the first to show that biallelic LOF variants in CIB2 cause ARNSHL and not USH. In the era of precision medicine, providing the correct diagnosis (NSHL vs USH) is essential for patient care as it impacts potential intervention and prevention options for patients. Here, we provide evidence disqualifying CIB2 as an USH-causing gene.

A rare ANOS1 variant in siblings with Kallmann syndrome identified by whole exome sequencing.

Kallmann syndrome is a rare genetic condition causing congenital hypogonadotropic hypogonadism. It presents with delayed puberty, anosmia, and infertility. Here, we set out to identify a causative DNA variant for Kallmann syndrome in two affected brothers of Hispanic ancestry. The male siblings presented with a clinical diagnosis of Kallmann syndrome (anosmia, delayed puberty, azoospermia, and undetectable luteinizing hormone and follicle stimulating hormone levels). Genetic variations were investigated by whole exome sequencing. Potentially pathogenic variants were filtered and prioritized followed by validation by Sanger sequencing in the two brothers and their mother. A pathogenic variant was identified in the ANOS1 gene on the X chromosome: c.1267C>T; both brothers were hemizygous, and their mother was heterozygous for the variant. The variant is a single nucleotide change that introduces a stop codon in exon 9 (p.R423*), likely producing a truncated variant of the protein. This variant has only been reported twice in the literature, in the setting of finding genetic causes for other conditions. This result supports the clinical value of whole exome sequencing for identification of genetic pathogenic variants. Genetic diagnosis is the essential first step for genetic counseling, preimplantation diagnosis, and research for a potential treatment.

LPS-induced Src family kinases activity mediates IL-10 production through activation of STAT3 in peripheral blood mononuclear cells of patients with Behçet's Disease.

Behçet's disease (BD) is achronic inflammatory disorder characterized by recurrent oral and genital ulcers, uveitis and skin lesions. Although,the pathogenesis of BD remains poorly understood, excessive or dysregulatedcytokine production including IL-10 is associated with BD. Revealing the key molecular mechanism by which IL-10 expression is regulated is crucial to understanding the pathogenesis of BD. The aim of this study was to investigate whether Src family kinases (SFKs) are upstream mediators of STAT3/IL-10 pathway in peripheral blood mono nuclear cells(PBMCs) of active BD patients.Twenty active BD patients and twenty healthy subjects used as control were included in the study. PBMCs were isolated from total blood by density gradient centrifugation.Western blot and ELISA methods were applied to analyzelipopolysaccharide (LPS)-induced SFKs/STAT3/IL10 signaling pathway in BD.Inhibition of SFKs activity suppressed LPS-induced IL-10 production in PBMCs fromboth controls and active BD patients. Similarly, blockage of STAT3 activation abrogated LPS-induced IL-10 production. However, LPS-induced STAT3 activation required for IL-10 production was found to be dependent on SFKs activity as LPS-induced STAT3 phosphorylation was reduced by the inhibition of SFKs activity in PBMCs of active BD patients.SFKs activity is essential for LPS-induced STAT3/IL-10 pathway in PBMCs of active BD patients. Manipulation of the SFKs activity may offer a novel therapeutic approach for BD.

Cytomegalovirus and Epstein-Barr virus reactivation in the intensive care unit.

AIM: The purpose of this work was to evaluate the reactivation of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in immunocompetent patients in the intensive care unit (ICU) and to identify risk factors associated with reactivation. MATERIALS AND METHODS: In this observational prospective study, 60 adult immunocompetent patients who stayed at least 7 days in an ICU were evaluated. During hospitalization, the viral load was monitored at admission and on day 7 with polymerase chain reaction to detect viral reactivation and weekly thereafter on days 14, 21, and 28 if hospitalization continued. RESULTS: The mean age of patients was 63.3 years (±23.4 years) and 34 (56.7 %) of them were male. Mean APACHE II scores for patients was 25 at admission. Of these patients, 28 were hospitalized in the internal ICU and 32 were hospitalized in the anesthesiology ICU. CMV/EBV reactivation was found in 17 individuals (12 for EBV, 3 for CMV, and 2 for both). The median high-sensitive C-reactive protein value in patients with CMV reactivation was significantly higher than in those patients without CMV reactivation (p = 0.037). EBV reactivation was statistically higher in patients with mechanical ventilation compared to patients without mechanical ventilation (p = 0.023). EBV reactivation in patients with fever was found to be statistically higher than in the patients without fever (p = 0.035). CONCLUSION: There is a need for extended studies with a larger number of patients from specific groups to better understand the reactivation frequency and identify risk factors. EBV and CMV reactivation should be taken into consideration in critically ill patients with fever, without specific symptoms and unresponsive to the treatment.

Prevalence and mutations of ß-thalassemia trait and abnormal hemoglobins in premarital screening in Çanakkale province, Turkey.

The prevalence of ß-thalassemia (ß-thal) carriers in Turkey varies according to region but in general it is 2.0%. Çanakkale is a city in the Aegean region of Turkey but no study about ß-thal frequency in Çanakkale has been published to date. In this study, we aimed to investigate the frequency of ß-thal mutations in this province. A total of 4452 couples (8904 individuals) applied for premarital thalassemia scans at the Çanakkale State Health Directorate Laboratory between January 2008 and June 2012 and scanning was done with high performance liquid chromatography (HPLC). Of 125 ß-thal carriers seen at the Medical Genetics Clinic, Çanakkale Onsekiz Mart University, Çanakkale, Turkey, for genetic counseling, 46 participated in the study. The remaining 79 patients could not be reached. The prevalence for ß-thal carriers in Çanakkale was identified as 1.4% (125/8904). One couple were both ß-thal carriers. ß-Globin gene analysis of 46 carriers found the total frequency of the three most common mutations was 45.6%. These mutations were found to be HBB: c.93-21G>A [IVS-I-110 (G>A)], 26.08% (12/46); HBB: c.17_ 18delCT [codon 5 (‒CT)], 10.85% (5/46); HBB: c.20delA [codon 6 (‒A)] 8.69% (4/46). This is the first report on the frequency and mutation profiles of ß-thal for Çanakkale. The incidence of ß-thal carriers in Çanakkale is below the average for Turkey. The most frequently observed mutation profile and rate of ß-thal in our region is different from the other regions of Turkey.

Variations in Multiple Syndromic Deafness Genes Mimic Non-syndromic Hearing Loss.

The genetics of both syndromic (SHL) and non-syndromic hearing loss (NSHL) is characterized by a high degree of genetic heterogeneity. We analyzed whole exome sequencing data of 102 unrelated probands with apparently NSHL without a causative variant in known NSHL genes. We detected five causative variants in different SHL genes (SOX10, MITF, PTPN11, CHD7, and KMT2D) in five (4.9%) probands. Clinical re-evaluation of these probands shows that some of them have subtle syndromic findings, while none of them meets clinical criteria for the diagnosis of the associated syndrome (Waardenburg (SOX10 and MITF), Kallmann (CHD7 and SOX10), Noonan/LEOPARD (PTPN11), CHARGE (CHD7), or Kabuki (KMT2D). This study demonstrates that individuals who are evaluated for NSHL can have pathogenic variants in SHL genes that are not usually considered for etiologic studies.

Vertebrobasilar insufficiency and gamma-glutamyltransferase: An emerging relationship demonstrating inflammation and atherosclerosis.

OBJECTIVES: Vertebrobasilar insufficiency (VBI) is a pathology arising from the reduction in flow rate of vertebral arteries and mainly caused by inflammation and atherosclerosis. Gamma-glutamyltransferase (GGT) is a marker which has been recently recognized as a marker of inflammation and atherosclerosis. We aimed to investigate the relationship between GGT levels and VBI for the first time. METHODS: In this cross-sectional study, of 3100 subjects who had vertebrobasilar doppler ultrasonography (VBU) were evaluated and 1042 of them who met the inclusion criterias were included. VBU reports, GGT levels, blood chemistry, lipid profile were received from patients' files. Patients were evaluated according to VBU measurements and divided into two groups,VBI and non-VBI. RESULTS: Mean vertebral arterial blood flow volume values were 149.99±32.93 mL/m in VBI group and 286.88 ± 70.98 mL/m in non-VBI group. Mean GGT and CRP values were significantly higher in the VBI group than in the non-VBY group (p < 0.001) ( p < 0.001), respectively. Vertebral artery blood flow volume was negatively correlated with GGT (r: -0.208, p < 0.001) and CRP (r: -0.119, p < 0.001). CONCLUSION: We demonstrated a significant correlation between serum GGT levels and VBI. In addition, higher GGT level was an independent risk factor for the presence of vertebrobasilar system inflammation and atherosclerosis (Tab. 2, Fig. 3, Ref. 27).

The association between mean platelet volume and infants with meconium stained amniotic fluid.

OBJECTIVE: The exact pathophysiology of meconium passage into the amniotic fluid is unknown, but it is frequently associated with fetal hypoxia. The mean platelet volume (MPV) seems to be a marker of platelet production and consumption and may be related to the severity of some diseases associated with bone marrow, hypoxia, and perinatal infections. We aimed to investigate the association between MPV levels and meconium-stained amniotic fluid (MSAF) in infants. PATIENTS AND METHODS: MPV, serum-reactive protein and hemoglobin levels, and leukocyte and thrombocyte counts were measured in 106 infants with MSAF and a comparison group of 78 healthy control infants. RESULTS: The mean MPV values of the infants with MSAF were statistically significantly lower than those of the control group (p < 0.001). There was no statistically significant difference in the hemoglobin levels or leukocyte and thrombocyte counts in the study group compared to the control group (p > 0.05). There was also no statistically significant difference in the MPV levels of the infants with meconium aspiration syndrome (MAS) compared to the infants with MSAF without MAS (p = 0.107). The optimal cut-off value for the MPV was 9.90 fl (area under the curve [AUC: 0.788]) in the infants with MSAF, with a sensitivity of 78.1% and specificity of 74.3%. CONCLUSIONS: Our data suggest that the MPV levels of infants with MSAF were significantly lower than those of healthy infants. This might be associated with a hypoxic process. However, the MPV levels of infants with MSAF and MAS were statistically similar. Thus, the MPV level could not be used to detect patients with or without severe disease.

Mean platelet volume in hepatitis A.

OBJECTIVE: Hepatitis A virus (HAV) still continues to be a serious public health problem worldwide. Mean platelet volume (MPV) is a marker of platelet function and activation. This study aimed to evaluate the relationship between MPV in acute hepatitis A patients as compared to the control group and to assess MPV as an acute phase reactant in acute hepatitis A. PATIENTS AND METHODS: Seventy-six patients were enrolled in this study. The control group consisted of 41 healthy age- and sex-matched individuals. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, prothrombin time (PT), platelet count (PC), serum albumin (ALB), and mean platelet volume (MPV) levels were recorded. The diagnosis of HAV infection was based on anti-HAV Ig M positivity. RESULTS: The mean levels of MPV in the study group were significantly statistically lower than in the control group (p < 0.001). The MPV levels revealed no correlation with the ALT, AST, ALP, and GGT levels (p > 0.05), but the MPV levels correlated with the platelet counts (p < 0.05). A 9.75 fL [area under the curve (AUC: 0.756)] optimal cutoff level of MPV with a sensitivity of 69.7% and specificity of 68.3% was determined in the children with acute hepatitis A. CONCLUSIONS: MPV levels were significantly lower in the patients with acute hepatitis A as compared to the healthy control group. This study demonstrated that MPV may be a negative acute phase reactant for acute hepatitis A. Further studies will explain the role that MPV plays in inflammation and other viral infections.

Are blood pressure values compatible with medication adherence in hypertensive patients?

BACKGROUND AND AIM: In the management of hypertension (HT), maintaining the medication adherence with treatment is as important as starting treatment. Studies have shown that the majority of patients taking medication do not reach their target values. This study aimed to investigate the relationship between the patient medication adherence and blood pressure (BP) values and reflection to general well-being. MATERIAL AND METHODS: The study included 259 primary HT patients. The patients with BP measurements completed the Medication Adherence Self-Efficacy Scale-Short Form 13 and the World Health Organization-5 (WHO-5) well-being index. A Holter device was attached, and 24 h BP monitoring was completed. RESULTS: The mean points for medication adherence scale was 29.2 ± 10.3 (1-40) and mean WHO-5 points was 13.7 ± 4.6 (4-25) for patients. Clinical mean systolic BP was 140.0 ± 12.6 and diastolic 84.8 ± 9.0 mm Hg, while 24 h mean BP was systolic 119.5 ± 10.6 and diastolic 73.3 ± 8.1 mm Hg. While there was negative correlation between medication adherence scale scores and clinical systolic BP (r = -0.171; P = 0.006), there was no correlation with other BP readings. There was no correlation with the WHO-5 score and clinical readings, though there was a positive correlation between ambulatory mean systolic and diastolic BP (r = 0.141; P = 0.023 and r = 0.123; P = 0.049, respectively). There was positive correlation between the patient's medication adherence scores and the WHO-5 scores (r = 0.141; P = 0.023). CONCLUSION: When clinicians assess medication adherence of patients, they should benefit from objective BP measurements and scales. Subjective and objective findings are important while making clinical decision.

The MEFV gene pathogenic variants and phenotype-genotype correlation in children with familial Mediterranean fever in the Çanakkale population.

The aim of the current study was to determine the frequency of the Mediterranean fever (MEFV) gene pathogenic variants in 60 children diagnosed with familial Mediterranean fever (FMF) and to compare the phenotype-genotype correlation. Genomic DNA was isolated by the spin-column method from peripheral blood samples (collected in vacutainers containing EDTA) and buccal smears. The MEFV gene profiles for the current FMF cohort were genotyped by pyrosequencing and direct Sanger sequencing techniques for the target pathogenic variants. The most prominent clinical symptoms were abdominal pain (53.4%), fever (23.4%) and arthritis (23.3%). Eighteen different pathogenic variants were identified and the most frequent were p.Met694Val (20.0%), p.Glu148Gln (13.3%), p.Met680 Ile (11.7%) and p.Arg202Gln (11.7%). Abdominal pain, fever and arthritis were the most common presenting clinical characteristics. Results showed that not only clinical characteristics, but also genotyping of the MEFV gene is needed to establish the correct diagnosis of FMF in children and other family members.

Investigation of the effects of oleuropein rich diet on rat enteric bacterial flora.

OBJECTIVES AND BACKGROUND: Oleuropein is a phenolic compound of olive leaves. Enteric bacterial flora is very important for human health and diet is a directly affecting factor of enteric bacterial flora composition. In this study, it was hypothesized that oleuropein could reduce total aerobic bacterial count in rat caecal flora. METHODS: Twenty adult, male, Wistar albino rats were randomly divided into two groups. Group C (n=10) was fed with standard rat chow and water for 30 days. Group O (n=10) received olive leaf extract 20 mg/kg/day by intragastric gavage in addition to standard rat chow and water for 30 days. One gram of caecal content was collected from each rat and then consecutive 10-fold serial dilutions were prepared with a final concentration of 10-8. Then 0.1 ml of each dilution were spread onto the surfaces of Plate Count Agar and Violet Red Bile Glucose Agar to enumerate the aerobic enteric bacteria. RESULTS: Total aerobic bacterial counts of Group O were significantly lower than of Group C in all agar plates inoculated with ceacal samples for every dilution (p<0.05). CONCLUSION: Adding oleuropein to enteral feeding solutions of critically ill patients may be adventageous in the presence of clinical conditions predisposing to bacterial translocation by reducing enteric bacterial counts (Tab. 1, Ref. 32).

A Mayan founder mutation is a common cause of deafness in Guatemala.

Over 5% of the world's population has varying degrees of hearing loss. Mutations in GJB2 are the most common cause of autosomal recessive non-syndromic hearing loss (ARNHL) in many populations. The frequency and type of mutations are influenced by ethnicity. Guatemala is a multi-ethnic country with four major populations: Maya, Ladino, Xinca, and Garifuna. To determine the mutation profile of GJB2 in a ARNHL population from Guatemala, we sequenced both exons of GJB2 in 133 unrelated families. A total of six pathogenic variants were detected. The most frequent pathogenic variant is c.131G>A (p.Trp44*) detected in 21 of 266 alleles. We show that c.131G>A is associated with a conserved haplotype in Guatemala suggesting a single founder. The majority of Mayan population lives in the west region of the country from where all c.131G>A carriers originated. Further analysis of genome-wide variation of individuals carrying the c.131G>A mutation compared with those of Native American, European, and African populations shows a close match with the Mayan population.

Attention deficit and hyperactivity disorder and infantile colic.

AIM: Attention deficit and hyperactivity disorder (ADHD) and infantile colic (IC) are heterogeneous diseases which's cause are unknown. Besides the different hypotheses in the etiology of both disorders maldevelopment in the metabolism of neurotransmitters in the central nervous system have been implicated. The goal of this study is to investigate the relationship between IC and ADHD due to possible common etiological factor as maldevelopment in neurochemical process. METHODS: A case-control study was carried out. The sample included 114 (77.2% male) children who were medically diagnosed with AD/HD and 149 (67.1% male) healthy children who were chosen from the same hospital's pediatric clinic as the control group. Parents and teachers completed the Conners Parent Rating Scale (CPRS), Conners Teacher Rating Scale (CTRS) and the patients were evaluated with The Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). The parents were asked questions on a survey form filled out. IC was defined according to Wessel's modified criteria. RESULTS: The mean age of AD/HD group was 10.14±2.48 years and 9.94±2.34 years in the non-AD/HD group. The rate of IC in AD/HD and non-AD/HD groups were 50.0% and 30.2%, respectively and the difference was statistically significant between two groups (P=0.001). Duration of IC was similar in the groups (P=143). CONCLUSION: IC may be a postnatal risk factor and marker for AD/HD during childhood. Both diseases may have a common mechanism. Such infants need to be examined and followed up more intensively.